Four molecular variants of rat alpha-fetoprotein (AFP) have been identified based on their concanavalin A-affinity (ConA-A) and isoelectric points. The ConA-A molecular variants present in amniotic fluid, and in sera of fetal/newborn rats, primary and transplantable hepatoma-bearing rats and rats during 3'-MDAB hepatocarcinogenesis have been measured previously. Each of the electrophoretic molecular variants will be quantified in amniotic fluid, fetal and newborn rat serum, serum of rats undergoing 3'-MDAB hepatocarcinogenesis, serum of rats bearing 3'-MDAB-induced primary hepatomas, serum of rats bearing transplantable hepatomas derived from the 3'-MDAB-induced tumors, serum of subtotally-hepatectomized rats and serum of rats exposed to hepatotoxins (CC14, galactosamine). ConA-A molecular variants will be measured in sera of adult rats, rats following exposure to hepatotoxins and rats following subtotal hepatectomy. The electrophoretic variants present in each of the ConA-A molecular variants of the AFP in amniotic fluid and in sera obtained from fetal rats, new-born rats and hepatoma-bearing rats will be measured. Each of the four known molecular variants will be isolated from sera of newborn rats, primary hepatoma-bearing and transplantable hepatoma-bearing rats. The purified variants will be characterized and compared physicochemically and immunologically. The metabolism of the conA-A and electrophoretic AFP molecular variants will be compared in normal adult rats. Half-lives of the molecular variants will be calculated, and the possibility of interconversion among the molecular variants will be tested. The objectives of this investigation are to: 1) establish the pattern of AFP molecular variants present during different physiologic and pathologic conditions, 2) determine if there are differences in the metabolism of the molecular variants following secretion from the liver cell, and 3) determine the physicochemical differences among the various molecular forms of rat AFP.